New Research in Chemotherapy-Induced Nausea and Vomiting (CINV)

For cancer patients undergoing chemotherapy, few side effects are as common and debilitating as the nausea and vomiting that often accompany the chemo regimen. As cancer researchers learn more about the mechanisms that can trigger chemotherapy-induced nausea and vomiting (CINV), treatment guidelines increasingly recommend combination antiemetic regimens that inhibit multiple molecular pathways. One of the more commonly recommended regimens for preventing and treating CINV is one that combines a selective 5-HT3 receptor antagonist, a neurokinin-1 receptor antagonist (NK1RA), and dexamethasone.


Recently, at the Multinational Association of Supportive Care in Cancer (MASCC) Congress in Washington, DC, our team presented results from the first head-to-head study comparing NK1RA regimens in the HEC setting. This was a Phase III, randomized, double-blind, study conducted in 828 chemotherapy-naïve Asian patients who were receiving cisplatin-based HEC as first-line therapy. We found that a single oral dose of netupitant/palonestron (NEPA) the first fixed combination of the selective 5-HT3 receptor antagonist palonosetron (0.5mg), and NK1RA netupitant (300 mg) was non-inferior to (i.e., at least as effective as) a three-day course of oral aprepitant and granisteron (APR/GRAN) in preventing CINV.


Patients in the study were randomized to receive either a single dose of NEPA on day 1 or APR/GRAN on days 1-3. All patients received the oral dexamethasone on days 1-4. The study’s primary efficacy endpoint was complete response (CR) as defined by no emesis (vomiting) or use of rescue medication during the overall (0-120 hours after chemotherapy) phase of CINV, which comprises both the acute (0-24 hours) and the delayed (25-120 hours) phases. Among the 412 patients receiving NEPA, 73.8% achieved a CR, compared to 72.4% of the 418 patients in the APR/GRAN group. Additionally, the daily rates of patients experiencing CINV events (emesis and/or rescue medication use) remained between 13-15% in the APR/GRAN group, yet declined from 16% to 8% over five days in the NEPA group. The safety profile of NEPA was comparable to that of APR/GRAN.


The availability of an oral antiemetic targeting two antiemetic pathways in a convenient single capsule can make chemotherapy less burdensome for patients with cancer, especially those undergoing HEC regimens. When administered as a single oral dose only once per cycle, such a combination therapy can make it easier to take the anti-CINV medication as prescribed, particularly when treatment guidelines recommend targeting two critical pathways. The rationale for NEPA is based on the fact that palonosetron prevents nausea and vomiting during the acute phase of CINV and netupitant does so during both the acute and delayed phases. Oral NEPA has been approved in the United States (where it is marketed under the Akynzeo® brand name) and Europe for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of cancer chemotherapy, including, but not limited to, HEC. Its approval was based on evidence of superior CINV prevention compared to palonosetron among patients receiving cisplatin- and Adriamycin/cyclophosphamide (AC)-based chemotherapy.


NEPA is recommended by various antiemetic guidelines, including those issued by the National Comprehensive Cancer Network (NCCN), the American Society for Clinical Oncology (ASCO), and joint guidelines from MASCC and the European Society of Medical Oncology (ESMO). Presumably, more widespread use of NEPA would help greater numbers of patients avoid CINV, relieving them of one of the more debilitating complications of anticancer therapy.

Topics: Cancer research, CINV, antiemetics for chemo, chemo-induced nausea, chemo-induced vomiting

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